Examining Pricing and Availability for Neglected Tropical Disease Therapies in the United States

Abstract

Background

Neglected tropical diseases primarily affect vulnerable populations in low-resource settings worldwide. In the United States, neglected tropical diseases such as Chagas, soil-transmitted helminthiases, and other infections historically affected immigrants but are increasingly relevant for US residents with climate change. We examined the pricing, prescribing rates, and supply of therapies used to treat neglected tropical diseases in the United States and their implications for accessibility and patient care.

Methods

A retrospective analysis of prescription rates, wholesale acquisition costs, and shortages was conducted for 11 treatment products from 2019 to 2024, aggregating data from Symphony Metys, First Databank, NAVLIN, Red Book, and the University of Utah Drug Information Service.

Results

While prices for most neglected tropical diseases were stable, albendazole prices decreased by 78% while mebendazole prices rose by 60%. Miltefosine remained expensive at $48 000 per treatment course. There are limited manufacturers of neglected tropical disease treatments in the United States, increasing vulnerability to shortages.

Conclusions

Addressing pricing irregularities and supply vulnerabilities requires legislative and policy interventions to enhance generic competition, expand public manufacturing, and strengthen supply chains. Such measures are critical to ensuring affordable and accessible treatment options for neglected tropical diseases in the United States.

Pricing and shortages of neglected tropical disease therapies in the United States limit treatment access. Albendazole costs declined, but mebendazole and miltefosine remain expensive. Limited manufacturers increase supply vulnerabilities. Policy interventions, such as public manufacturing and supply chain strengthening, are essential for ensuring affordable, accessible treatments.

Graphical Abstract

Graphical Abstract.

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Neglected tropical diseases (NTDs) are a group of parasitic, viral, and bacterial infections that primarily affect impoverished communities worldwide and can be associated with broad health and socioeconomic consequences [1, 2]. These diseases limit education, reduce economic productivity, and in some diseases impair cognitive development [2, 3]. The World Health Organization estimates that the global impact of NTDs includes 19 million disability-adjusted life-years lost annually and 200 000 deaths [1, 2]. Despite their global impact, NTDs are often overlooked in drug development initiatives led by for-profit manufacturers. Organizations such as the Drugs for Neglected Diseases Initiative work to address these gaps, yet reports have documented inadequate availability of and access to diagnostics, treatments, and prevention efforts in low- and middle-income countries [1].

In high-income countries such as the United States, NTD prevalence is rising due to environmental changes, immigration, and expanded global travel [4]. While NTD transmission in the United States remains lower than in low- and middle-income countries, it is more likely to affect vulnerable populations, such as immigrants and people experiencing homelessness [5]. Higher temperatures in the southern half of the United States have been linked to outbreaks for NTDs such as dengue, and an estimated 3 to 4 million people in US Gulf Coast states have been affected by at least 1 NTD [5]. For example, Chagas disease affects an estimated 300 000 individuals in the United States, with around 10 000 new cases annually, yet <1% have been reported to receive the appropriate antiparasitic treatment [6].

Table 1 provides an overview of key NTDs discussed in this article and their prevalence in the United States, encompassing imported and autochthonous cases. Estimates for many NTDs, including soil-transmitted helminthiasis, remain imprecise due to a lack of recent nationally representative surveillance and inconsistent reporting [19, 20]. Soil-transmitted helminthiasis, thought to be the most widespread NTD, affects an estimated 4 to 5 million individuals, [14, 15] with the second-highest burden being Chagas disease with an estimated prevalence of 300 000 cases [7]. Cysticercosis led to 1320 to 5050 cases of medically attended neurocysticercosis annually [17, 18]. These estimates likely underrepresent the true prevalence of cysticercosis and Taenia solium infection as only neurocysticercosis data were available [18]. Leishmaniasis has low prevalence rates, with an annual incidence estimated at 150 cases [8, 9]. Leprosy similarly has an estimated annual incidence between 120 and 230 cases [10, 11]. Echinococcosis and rabies remain rare, with only about 5 cases each year [12, 13]. Schistosomiasis is also considered uncommon, with the majority of cases being imported [16]. The seroprevalence among refugees and immigrants is better studied with, for example, a 27.7% seropositivity rate for Schistosoma mansoni antibodies found among Brazilian immigrants [21]. Surveillance data may underestimate disease prevalence, particularly among marginalized groups with limited health care access.

Table 1.

Epidemiology of Neglected Tropical Diseases in the United States

Condition	Estimated Prevalence	Estimated Incidence per Year	Sources
Chagas disease	300 000	Not well documented	Irish et al (2022) [7]
Leishmaniasis	Unclear but thought to be low prevalence	∼150	Curtin and Aronson (2021) [8]; McIlwee et al (2018) [9]
Leprosy	Unclear	120–230	CDC [10]; National Hansen's Disease Program (2024) [11]
Echinococcosis	Very rare	5	Katz and Pan (1958) [12]
Rabies	Very rare	5	Ma et al (2023) [13]
Soil-transmitted helminthiases (ascariasis, toxocariasis, strongyloidiasis, and trichonellosis)	4–5 million	Not well documented	Lynn et al (2021) [14]; Hotez (2016) [15]
Schistosomiasis	Rare	Rare	Verjee (2019) [16]
Cysticercosis	0.5%–3% in select populations	∼1320–5050 of neurocysticercosis	Serpa and White (2012) [17], Cantey et al (2014) [18]

Abbreviation: CDC, Centers for Disease Control and Prevention.

The US health care system must be prepared for and respond to patients with NTDs [22]. However, growing reports highlight serious challenges with the availability of NTD treatment products, including high drug prices, drug shortages, and limited generic alternatives [23–27]. Research also suggests that the high cost of these medications has directly affected the diagnosis and treatment of conditions such as soil-transmitted helminthiases, leading to reduced screening, lower-than-recommended dosing, and off-label prescribing of nonapproved anthelmintics [24, 28]. The lack of affordable treatment options in the United States increases the risk of morbidity and mortality among affected individuals, leading to broader public health consequences. In response, recent legislative efforts, such as the STOP Neglected Diseases of Poverty Act proposed in Congress in 2023 (118th Congress, S 324), have tried to address the growing need for accessible and affordable NTD treatments [29].

We sought to examine the pricing trends and prescription rates of treatment products across NTDs within the US health care system. We evaluated the historical and current pricing of essential products to identify critical areas in which interventions may be necessary to ensure the continued availability and affordability of essential NTD treatments.

METHODS

This retrospective observational study analyzed NTD product pricing, prescribing trends, and shortages in the United States from 2019 to 2024.

Treatment Product Cohort Selection

NTDs were identified per the official World Health Organization list and confirmed for relevance in the United States via the Centers for Disease Control and Prevention (CDC) National Notifiable Diseases Surveillance System [1, 30], which verified the presence of dengue, Hansen disease, and rabies in the United States [30]. The CDC Yellow Book 2024 and a PubMed literature search with a 10-year date filter provided additional information on infections with documented impact on US populations, confirming the presence of chikungunya, Chagas disease, echinococcosis, food-borne trematodes, leishmaniasis, lymphatic filariasis, onchocerciasis, scabies, schistosomiasis, soil-transmitted helminthiases, and cysticercosis [31].

Oral and injectable treatment products available on the US market in the last decade were included if they were Food and Drug Administration (FDA) approved for NTD treatment and had no other primary indications outside NTDs. We included brand-name and generic formulations.

We used treatment recommendations for each NTD outlined in the CDC Yellow Book 2024 to identify eligible treatment products. For each treatment product recommended, we used the FDA Drug Approvals and Databases to confirm US approval status and evaluate each product's compliance with our inclusion criteria. Searches were conducted in Drugs@FDA, FDA Orange Book, and the FDA Purple Book.

Data Collection

We collected wholesale acquisition cost (WAC) per unit data from Q1 2019 to Q4 2024 from Navlin, Red Book, and First Databank via Analysource, which are commercial drug-pricing compendia that report wholesale WAC data as provided by pharmaceutical manufacturers. To ensure accuracy and consistency, pricing data for each product were cross-checked across all 3 sources. All prices presented in this article were consistent across NAVLIN, Red Book, and FDB at the time of data extraction. In some instances, certain products, particularly discontinued drugs, appeared in 1 database (eg, First Databank) but were not available in others (eg, Red Book or Navlin). In such cases, First Databank was used as the reference source due to its broader historical coverage. Discontinued NTD treatments were identified by FDA Orange Book archives and pharmaceutical manufacturer websites.

Prescription rate data for Q1 2019 to Q4 2024 were sourced from Symphony Metys, which provides quarterly prescription data by generic name. Symphony Metys is a commercial claims database that aggregates prescription-dispensing data from a range of retail and mail-order pharmacies across the United States. It captures volume and timing of drug dispensation at the national drug code level.

Drug shortage data were obtained from the University of Utah Drug Information Service, which defines a shortage as any supply issue affecting drug dispensing or patient care [32, 33]. The service collects voluntary reports of shortages, verifies them through manufacturer contacts, and posts details on a publicly available website offered through ASHP (https://www.ashp.org/drug-shortages/current-shortages), including affected products, reasons for shortages, and management strategies [34–36]. Shortages are considered resolved when all suppliers have restored availability or discontinued the product.

Nonoral formulations for ivermectin, the only drug in our analysis with multiple formulations, were excluded as they are not used for NTDs. Rabies vaccine was included in this analysis for its use in postexposure prophylaxis.

Data Analysis

Data were analyzed by comparing pricing data and prescription rates across NTD treatment products. For treatment products with multiple manufacturers (albendazole, ivermectin, praziquantel, rabies immunoglobulin, and rabies vaccine), we calculated weighted average prices using a standard weighted average formula based on WAC per unit cost and total prescription volume for each national drug code during the specified periods. For rabies immunoglobulin and rabies vaccine, we calculated weighted average WAC per international unit using the actual vial sizes and unit strengths dispensed. The resulting annual weighted averages reflect shifts in price and use patterns during the study period. Treatment cost estimates were based on the exact unit quantity required for a full course, without accounting for packaging constraints.

RESULTS

The following 11 products indicated for these conditions and available in the United States were selected for analysis: albendazole, benznidazole, clofazimine, ivermectin, mebendazole, miltefosine, nifurtimox, praziquantel, pyrantel pamoate, rabies vaccines, and rabies immunoglobulin. We excluded dapsone and rifampicin, which are used to treat leprosy, as they have primary clinical indications outside NTDs. Several NTDs with established prevalence in the United States, such as dengue and chikungunya, are managed symptomatically and lack specific drug treatments. Cost estimates are intended as WAC-based, standardized, comparative benchmarks for guideline-recommended treatment courses across products, rather than estimates of real-world out-of-pocket or payer costs. For all weight-based treatments, estimated costs are based on a 70-kg individual for comparability.

Soil-Transmitted Helminthiases, Echinococcosis, Cysticercosis, and Scabies

Albendazole, ivermectin, pyrantel pamoate, and mebendazole treat soil-transmitted helminthiases. For the purposes of comparability across treatment products in the figures and text, total cost estimates are calculated by the standard treatment courses for soil-transmitted helminthiases. However, we note that albendazole is used for other parasitic infections, such as neurocysticercosis and hydatid disease, and ivermectin in the treatment of resistant and crusted scabies.

Albendazole showed a 78% decline in its weighted average price per pill from $173.99 in 2019 to $38.85 in 2024. Treatment courses for ascariasis, whipworm, and hookworm with albendazole typically require 2 to 6 pills [37].

Mebendazole's weighted average price per pill rose over time. The Vermox formulation of mebendazole was priced at $4.93 per pill but discontinued in 2011. Another brand-name version, Emverm, entered the US market in 2016, starting at $423.39 per pill, which increased by 60% to $678.80 by 2024. A typical treatment course of mebendazole requires 5 to 6 pills [37].

Ivermectin pricing remained nearly constant at $4.14 to $4.15. A total treatment of 4 to 15 pills would therefore amount to $16.60 to $62.25 (Figure 1) [37]. Last, pyrantel pamoate increased from $5.95 per 30-mL bottle in 2019 to $6.30 in 2024. The total course of treatment with pyrantel pamoate for a 70-kg individual cost about $3.37 in 2024 [37].

Figure 1.

Total price per treatment course in the United States, 2019–2024. *Calculations used the upper end of the recommended tablet range for treatment requirements. **Benznidazole treatment for adults is off-label; the 12.5-mg formulation of benznidazole, typically reserved for pediatric use, was excluded from the cost analysis to focus on formulations appropriate for a 70-kg adult for comparability across drugs. ***Nifurtimox calculations used the upper end of the recommended dose range and a 60-day treatment course to align with benznidazole; the 30-mg formulation of nifurtimox, primarily intended for pediatric use, was excluded from the cost analysis to maintain consistency with adult dosing comparisons.

Albendazole prescriptions have more than doubled, increasing from 100 850 pills in Q1 2019 to 237 571 in Q4 2024, with the highest use in Q3 2023 (242 957 pills; Figure 2). Albendazole experienced 2 shortages, once in 2004 and another in 2017, and both resolved in <5 months. Mebendazole prescriptions remained relatively stable, fluctuating between 17 000 and 25 000 pills per quarter. Ivermectin usage saw a spike during the COVID-19 pandemic, surging from 577 511 pills in Q1 2019 to 21.6 million pills in Q3 2021 [38]. This stabilized around 1.3 to 1.5 million pills per quarter from 2023 onward, still more than double pre-2020 levels. Pyrantel pamoate's quarterly prescriptions ranged from 103 750 to 181 056 bottles, demonstrating a small overall decline.

Figure 2.

Prescribing rates of treatments for soil-transmitted helminthiases in the United States, 2019–2024.

Schistosomiasis and Food-borne Trematodes

Praziquantel pricing remained stable from 2019 to 2024, with treatment costs of $333 for schistosomiasis (Figure 2). Praziquantel prescription rates steadily increased from 2019 to 2024 (Figure 3). No shortages of praziquantel have been noted since 2014, when the shortage was resolved in <3 months.

Figure 3.

Prescribing rates of benznidazole, nifurtimox, miltefosine, praziquantel, rabies immunoglobulin, and rabies vaccines in the United States, 2019–2024. Nifurtimox data were missing in Q1–Q4 2019 to 2020, Q2 2022, and Q3 2024. Rabies immunoglobulin data for Nebraska in Q3 2021 were excluded due to an unusually high prescription count (n = 805), which appeared to be inaccurate.

Chagas Disease

Benznidazole and nifurtimox pricing was stable ($2.50–$3.00 per pill). Given the treatment duration of 60 to 90 days for Chagas disease, a typical treatment course for a 70-kg individual would range from $630 to $1050 (Figure 2) [39]. Benznidazole prescriptions declined sharply from 12 609 pills in Q1 2019 to 63 in Q3 2023 before partially recovering in 2024, reaching 2489 pills in Q3 (Figure 3).

Nifurtimox prescription data were available starting at FDA approval in August 2020. Recorded use peaked at 2985 pills in Q4 2023 (Figure 3). Prescriptions fluctuated across quarters, with a general upward trend. There were no shortages reported of these drugs.

Leishmaniasis

Based on direct price-per-package estimates that each blister pack of miltefosine containing 28 capsules (50 mg) costs $16 000, a leishmaniasis treatment course of 150 mg in 3 divided doses over 28 days [40] would result in a $48 000 cost (Figure 2). Miltefosine prescriptions remained relatively stable from 2019 to 2023 at 2500 to 5200 pills per quarter. In 2024, use declined, reaching a low of 1624 pills in Q1 (Figure 3). No drug shortages were found.

Leprosy

Clofazimine is provided free of charge via Novartis through the federal National Hansen's Disease Program. Annual data reported by the program from 2022 and 2023 indicated that clofazimine prescription rates dropped from 56 100 capsules (50 mg) in 2022 to 36 000 in 2023.

Rabies

Human rabies immune globulin (HRIG) substantially increased in total price per treatment course from $269.98 in 2019 to $1474.60 in 2024. This increase occurred despite a relatively stable WAC for individual products, suggesting a shift toward higher-cost formulations, such as Imogam (2 mL, 150 IU) and HyperRAB (1 vial, 900 IU). Rabies immunoglobulin prescriptions remained low, fluctuating between 3 and 200 vials per quarter, with periodic increases around Q3 (Figure 3). A notable outlier in Q3 2021—805 prescriptions in Nebraska—was excluded due to suspected inaccuracy. The length of HRIG shortages averaged over 2 years.

The total price for rabies vaccine increased from $1425.40 in 2019 to $1590.14 in 2024, with the weighted average WAC per IU rising from $142.54 in 2019 to $159.01 in 2024, alongside growing use, particularly of the RabAvert formulation. Rabies vaccine prescriptions steadily increased, rising from 2799 vials in Q1 2019 to 10 767 in Q3 2024. Use nearly tripled between 2021 and 2024, with the highest recorded use in Q3 2024 (Figure 3). Rabies vaccines experienced frequent shortages, with disruptions almost annually from 2004 to 2019.

DISCUSSION

This study demonstrates the surprisingly high prices of treatment products for NTDs in the United States, alongside meaningful shortages. Despite most of these treatment products being off-patent and long established, they remain extremely expensive. Prescription rates for certain NTD treatment products appear modest when compared with available prevalence estimates, although these comparisons must be interpreted cautiously [6]. These findings underscore a critical access crisis, highlighting the urgent need for policy interventions to improve system-level affordability and availability.

The pricing trends observed for several treatment products underscore the central role of market competition on affordability. Weighted pricing of albendazole declined by 80% from 2019 to 2024, possibly due to the doubling of generic market entrants [41, 42]. By contrast, mebendazole prices increased by 60% in the same period following the introduction of a new brand-name version despite the active ingredient being decades old. This difference in pricing trends was reflected in prescribing patterns: albendazole prescriptions more than doubled, suggesting that the reduction in list price potentially contributed to increased access, as reflected by higher prescription volumes. Miltefosine, used to treat leishmaniasis, remained prohibitively expensive at $48 000 per treatment course and is available via only a single supplier [23]. These cost pressures may disproportionately affect public health programs and uninsured patients, who may have limited ability to absorb the cost of high-WAC therapies [24]. Yet insured patients may also face limited access to optimal therapies, delays in treatment, or reliance on less effective alternatives due to pricing pressures [6, 24, 43]. These findings illustrate the importance of encouraging market entry from multiple generic manufacturers to promote price reductions and improve access to essential NTD treatments.

The analysis of HRIG and rabies vaccine demonstrates the role of prescribing patterns in driving changes in the weighted average WAC, even when individual product prices remain stable. For HRIG, the weighted average WAC increased more than fivefold, from $269.98 in 2019 to $1474.60 in 2024, primarily due to increased use of higher-cost formulations such as HyperRAB (900 IU/vial) and Imogam (150 IU/2 mL). Similarly, the rabies vaccine's cost rose from $1425.40 to $1590.14 during the same period, driven by the growing use of the RabAvert formulation. These findings highlight the importance of monitoring prescribing patterns to control health care expenditures. Educational interventions can help guide physicians and patients toward cost-effective alternatives. Additionally, the CDC's 2022 revision to the rabies preexposure prophylaxis schedule [44], which reduced the number of required doses, may have contributed to increased prescribing of rabies vaccine. However, our analysis is focused on treatment-related use, and the rise in vaccine prescriptions appears to have started in 2021, prior to the guideline change, with no clear inflection point afterward. Further research using diagnosis-linked data is needed to determine whether the schedule change influenced broader vaccine use, particularly in preexposure contexts.

Access to many of these medications is further constrained by health system barriers that disproportionately affect at-risk populations. Specialty distribution requirements for benznidazole, nifurtimox, and miltefosine create additional hurdles for health care providers and patients, especially in resource-limited settings [6, 23, 45]. These challenges are compounded by the dependence on limited local diagnostic capacity and insufficient funding for uninsured patients [6].

Supply chain disruptions through shortages remain a key concern. The reliance on a limited number of manufacturers for treatment products increases the risk of future disruptions [36]. The stable supply of praziquantel since 2014 and only 1 recorded shortage in albendazole in the last 20 years suggest that robust supply chains are achievable with intentional diversification of suppliers. Ivermectin saw a dramatic surge in demand during the COVID-19 pandemic, peaking at 21.6 million pills dispensed in Q3 2021 due to off-label use, stabilizing at more than double prepandemic levels. Despite this, our data showed no recorded shortages. This highlights the importance of a stable supply chain when external pressures, such as public health crises, influence use patterns in ways that complicate access to NTD treatment.

There are several opportunities to address the persistent barriers to affordable and accessible NTD treatments. One approach is strategic prescribing, in which health care providers are made aware of and then opt for cost-effective alternatives when available. For example, ivermectin ($62 per treatment course) can be used for ascariasis and whipworm, while pyrantel pamoate ($3 per treatment course) remains a low-cost option for hookworm. However, physician education alone cannot resolve systemic affordability and supply issues. Furthermore, lower-cost options do not always offer equivalent clinical efficacy. For instance, pyrantel pamoate has been shown to be less effective than albendazole for hookworm [46, 47]. These trade-offs create difficult decisions for providers, particularly in resource-limited settings where affordability may take precedence over efficacy due to budget or supply constraints. As a result, structural reforms in addition to provider awareness are needed to ensure that essential medications are affordable and accessible.

Strengthening supply chains by diversifying manufacturers and implementing policies to ensure multiple suppliers for critical treatment products would reduce the risk of future shortages. Legislative efforts, such as the STOP Neglected Diseases of Poverty Act (S 324), could support this. This bill aims to address high treatment product costs, limited availability, and inadequate health care access by incentivizing research into affordable therapeutics, supporting federally qualified health centers, and adding provisions for expanding surveillance to strengthen supply chains and ensure timely access to treatment. If effectively implemented, such measures could alleviate some of the systemic challenges limiting NTD treatment product accessibility in the United States [29, 48].

In addition, while increasing generic competition is often viewed as a solution to high product costs, this strategy has not consistently ensured affordability. Multiple studies have highlighted that market consolidation among generic manufacturers, combined with limited financial incentives for producing low-demand treatments, has led to ongoing access challenges for essential treatment products such as albendazole, mebendazole, and miltefosine [25, 41]. Given these limitations, public manufacturing may provide a more effective solution by ensuring the production of essential NTD treatment products independent of profit-driven constraints. Public sector manufacturing initiatives, such as California's CalRx, have successfully produced affordable medications in cases for which market-driven solutions have failed [49]. Expanding public manufacturing to include key NTD treatments could stabilize supply chains, reduce costs, and improve access for underserved populations.

This study has several limitations that may influence its findings. WAC-based pricing may not accurately reflect real-world patient out-of-pocket expenses or insurance reimbursements. Actual costs may vary due to rebates, copay assistance, or packaging constraints. The exclusion of nonprescription access pathways, such as donation programs, may underrepresent alternative sources of medications. By focusing on treatment products with a primary indication for NTDs, this analysis may overlook accessibility challenges for multiuse treatments, such as dapsone for leprosy. Similarly, treatment products such as albendazole may be prescribed off-label or for non-NTD indications. Therefore, increases in prescription volume may reflect broader access for non-NTDs and could overestimate its use for NTD indications. The cost calculations in this study are likely to underestimate actual treatment expenses, as they assume that patients can purchase only the exact quantity needed for a treatment course. In practice, patients may be required to buy full units even if just a fraction is necessary, leading to higher out-of-pocket costs than estimated here. COVID-19–related disruptions may have temporarily distorted prescription trends, and the study did not include patient outcome data to directly assess health impacts.

CONCLUSION

Many essential NTD treatment products remain prohibitively expensive in the United States, despite being off-patent and long established. Our analysis highlights persistent challenges in drug pricing and supply chain stability. While some NTD therapies, such as albendazole, have become more affordable over the years, others, such as mebendazole and miltefosine, may pose financial barriers to treatment access, particularly in settings with limited reimbursement or institutional purchasing constraints. These patterns suggest broader structural challenges in ensuring consistent access to NTD therapies. Although strategic prescribing and generic entry may help mitigate some of these issues, coordinated policy responses are still needed. Public manufacturing initiatives may be an example of a sustainable solution.

Future research should explore how prescribing behavior aligns with disease burden using diagnosis-linked data and assess how policy interventions influence access and affordability over time. By addressing these systemic barriers, the United States can better prepare to meet the public health demands of NTDs and improve health equity for affected communities.

Notes

Acknowledgments. The authors thank Erin Fox for providing summaries of University of Utah Drug Information Service data.

Financial support. This work was supported by Arnold Ventures.